Asthma has recently been recognized as being mediated by an inflammatory response in the respiratory tract [DeMonchy, J., Am. Rev. Resp. Dis. 131: 373-376 (1985)]. Recent findings suggest that human T-lymphocytes play a major role in regulating the airway inflammation associated with allergic asthma [Frew, A. J., J. Allergy Clin. Immunol. 85: 533-539 (1990)] and chronic obstructive pulmonary disease [O'Connor, G. T., Am. Rev. Resp. Dis. 140: 225-252 (1989)].
In addition to the infiltration of other inflammatory cells into the pulmonary system, human asthmatics and atopics who are dual responders (i.e., show both early and late phase reactions) show a small but significant infiltration of T-lymphocytes following antigen challenge [Frew, A. J., and Kay, A. B., J. Immunol. 141: 4158-4164 (1988)]. More importantly, these recruited T-lymphocytes are almost entirely of the CD4.sup.+ (T-helper) type, and there appears to be a direct correlation between the influx of CD4.sup.+ cells, the influx of eosinophils, and the IgE-related allergic response in these individuals [Frew, A. M. and Kay, A. B., J. Immunol. 141: 4158-4164 (b 1988)]. In severe asthmatics, these CD4.sup.+ cells appear to be activated [Corrigan, C. J. and Kay, A. B. Am. Rev. Resp. Dis. 141: 970-977 (1990)] by virtue of the increase in IL-2 receptor positive cells. Thus, these cells are capable of producing cytokines (such as IL-3, IL-5, and granulocyte macrophage colony stimulating factor) which can directly affect the differentiation, maturation and activation state of the eosinophils and other inflammatory cells.
Rapamycin, a macrocyclic triene antibiotic produced by Streptomyces hygroscopicus [U.S. Pat. No. 3,929,992 ] has been shown to prevent the formation of humoral (IgE-like) antibodies in response to an albumin allergic challenge [Martel, R., Can. J. Physiol. Pharm. 55: 48 (1977)], inhibit murine T-cell activation [Strauch, M., FASEB 3: 3411 (1989)], and prolong survival time of organ grafts in histoincompatable rodents [Morris, R., Med. Sci. Res. 17:877 (1989)].